Paulovich collaborates in biomarker breakthrough

New detection method could speed identification of true cancer biomarkers

July 7, 2009

Dr. Mandy Paulovich and colleagues have found a new method for detecting and quantifying protein biomarkers in body fluids that may help researchers more rapidly zero in on real cancer biomarkers. Paulovich's Clinical Research Division lab is a performance site for the new method.

Photo by Susie Fitzhugh

A new method for detecting and quantifying protein biomarkers in body fluids may help researchers more rapidly zero in on real cancer biomarkers.

Dr. Mandy Paulovich’s lab and a multi-institute team of scientists are testing the new method, which may make it possible to screen multiple biomarkers in hundreds of patient samples, thus ensuring that only the strongest biomarker candidates will advance down the development pipeline. The method has the potential to increase accuracy in detecting real cancer biomarkers and is highly reproducible across laboratories and a variety of instruments so that cancer can be caught in its earliest stages.

The results of the Clinical Proteomic Technology Assessment for Cancer (CPTAC) study, which is sponsored by the National Cancer Institute and partner organizations, appeared online June 28, in Nature Biotechnology.

“The emergence of sensitive, quantitative targeted proteomic techniques holds the potential to greatly facilitate testing of large numbers of candidate biomarkers by allowing the development of new assays,” said Paulovich, whose Clinical Research Division lab was among seven performance sites. “This particular study was instrumental in demonstrating that such assays are robust and portable across laboratories. Our laboratory is involved in ongoing work with our collaborators to improve the sensitivity and throughput of this technology.”

The collaborative, multi-institute nature of this work was significant because many other technologies have yielded test results that vary greatly from one laboratory to the next.

The current biomarker discovery process typically identifies hundreds of candidate biomarkers in each study using small numbers of samples, leading to very high rate of invalid biomarkers. The biomarkers that are actually valid—that is, true biomarkers—must be culled from lengthy lists of candidates, a time-consuming and not always accurate process.

The CPTAC study demonstrated that new applications of existing proteomic techniques showed promise of greater accuracy. The findings suggest that two technologies—multiple reaction monitoring (MRM) coupled with stable isotope dilution mass spectrometry (SID-MS), which is a technique used by protein scientists to measure the abundance of a particular protein in a sample, may be suitable for use in preclinical studies to rapidly screen large numbers of candidate protein biomarkers in the hundreds of patient samples necessary for verification.

Clinical Proteomic Technologies for Cancer will make common samples and standardized protocols available through its reagents data portal, which can be accessed at http://proteomics.cancer.

"These findings are significant because they provide a potential solution for eliminating one of the major hurdles in validating protein biomarkers for clinical use,” said Dr. John Niederhuber, NCI director. “Thousands of cancer biomarkers are discovered every day, but only a handful ever makes it through clinical validation. This is a critical roadblock because biomarkers have the potential to allow doctors to detect cancer in the earliest stages, when treatment provides the greatest chances of survival. The key limiting factor to date in validating biomarkers for clinical use has been the lack of standardized technologies and methodologies in the biomarker discovery and validation process, and this research may solve that dilemma."

In addition to the Hutchinson Center, participating institutions include the Broad Institute of the Massachusetts Institute of Technology and Harvard; the University of Victoria; Skirball Institute at New York University; Monarch Life Sciences; University of California, San Francisco; Buck Institute for Age Research; and Vanderbilt University School of Medicine.